The DNF15S2 locus at 3p21 is transcribed in normal lung and small cell lung cancer

Naylor, Susan L.; Marshall, Angus; Hensel, Charles H.; Martinez, Pedro; Holley, Benjamin L.; Sakaguchi, Alan Y.

doi:10.1016/0888-7543(89)90342-x

Cited by 52 publications

(33 citation statements)

References 16 publications

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“…The average of our four determinations and reported values (21) is that each subunit contains about 377 ± 10 residues, a value in full agreement with its molecular weight determined by independent means (8,14,21 correlation between the presence of this locus and the expression ofan acylase in small cell lung carcinoma (23,28 (8,14), which indicate that substrates for the acylase bind to but are not hydrolyzed by the acylpeptide hydrolase and substrates for the acylpeptide hydrolase act as competitive inhibitors with the acylase, suggest that there may be some relationship of'the protein sequences of the two enzymes; however, conclusive evidence is still needed. Tentative location of the acylase as a segment of the acylpeptide hydrolase is supported by several observations:…”

Section: Methodssupporting

confidence: 55%

“…AGC GCCAGOCCGCGCTGA C CCC GTCACCACGCAGTACGGcGGcCaaTACCGGAC -9 agagcaaacatggagCGG CGGC CAcCGGGGCC TTAGC gcGCCGCC aGCACGGgGGtCg CTACCGGAC The complete acylpeptide hydrolase cDNA reported by with our amino acid analysis of porcine acylase and that from Mitta et al (9) strongly resembles the first part of DNF15S2 another laboratory (21) for the following amino acids (number cDNA (23), although there are some minor deletions (Fig. 1).…”

Section: Cggtcagggctgctgagcgagtcgaggaggcggcggctctgtatmentioning

confidence: 99%

“…Such examples have been described for proteins and peptides (31-33) but not for two cognate enzymes of different specificity. A question of particular interest is whether the acylpeptide hydrolase is actually expressed by the DNF15S2 locus and may be absent in some cases of renal cell carcinoma (24) and in small cell lung carcinoma (23). The absence of either the acylpeptide hydrolase or the acylase could lead to accumulation of an acetylated peptide growth factor with a possible role in cell transformation.…”

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confidence: 99%

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Genetic relationship between acylpeptide hydrolase and acylase, two hydrolytic enzymes with similar binding but different catalytic specificities.

Jones

Scaloni

Bossa

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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An 87% identity has been found between the reported cDNA sequence that encodes acylpeptide hydrolase (EC 3.4.19.1) [Mitta, M., Asada, K., Uchimura, Y., Kimizuka, F., Kato, I., Sakiyama, F. & Tsunasawa, S. (1989) J. Biochem. 106, 548-551] and a cDNA transcribed from a locus (DNFISS2) on the short arm ofhuman chromosome 3, reported by Naylor et al. [Naylor, S. L., Marshall, A., Hensel, C., Martinez, P. F., Holley, B. & Sakaguchi, A. Y. (1989) Genomics 4,[355][356][357][358][359][360][361]; the DNF15S2 locus suffers deletions in small cell lung carcinoma associated with a reduction or loss of acylase activity (EC 3.5.1.14). Acylpeptide hydrolase catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetylamino acid formed by acylpeptide hydrolase is further processed to acetate and a free amino acid by an acylase. The substrates for the acylpeptide hydrolase and the acylase behave in a reciprocal manner since acylpeptide hydrolase binds but does not process acetylamino acids and the acylase binds acetylpeptides but does not hydrolyze them; however, the two enzymes share the same specificity for the acyl group. These findings indicate some common functional features in the protein structures of these two enzymes. Since the gene coding for acylpeptide hydrolase is within the same region of human chromosome 3 (3p2l) that codes for the acylase and deletions at this locus are also associated with a decrease in acylase activity, there is a close genetic relationship between the two enzymes. There could also be a relationship between the expression of these two enzymes and acetylated peptide growth factors in some carcinomas.The various types of exopeptidases that act on the free NH2-terminal residues of polypeptides have been described in detail (1). The properties of a purified enzyme that cleaves an acetylated terminal amino acid from acetylated peptides (N-acylaminoacylpeptide hydrolase, EC 3.4.19.1, referred to here as acylpeptide hydrolase) have also been reported (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). For example, this enzyme catalyzes the hydrolysis of acetyltrialanine (Ac-Ala3-OH) to acetylalanine (Ac-Ala-OH) and dialanine (Ala2-OH). We reported that the rates of hydrolysis of different blocked peptide substrates varied considerably, depending on the nature of the first and second amino acids. Thus, there was a preference for Ac-Ala-, Ac-Met-, and Ac-Ser-at the blocked terminus (4). Comparison ofthis specificity with the sequences ofabout 100 known proteins acetylated at their NH2-terminal residues indicated that most of them began with Ac-Ala-, Ac-Met-, or Ac-Ser-(13). Furthermore, in these blocked proteins there was a preponderance of charged amino acid residues at the second position. Hence, the characteristics of the terminal sequence of these blocked proteins appear to resemble the substrate specificity ofthe acylpeptide hydrolase. The enzyme displays a broad spectrum with respect to the blocking group, since acetyl, chloroacetyl, formyl,...

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Section: Methodssupporting

confidence: 55%

Section: Cggtcagggctgctgagcgagtcgaggaggcggcggctctgtatmentioning

confidence: 99%

mentioning

confidence: 99%

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Genetic relationship between acylpeptide hydrolase and acylase, two hydrolytic enzymes with similar binding but different catalytic specificities.

Jones

Scaloni

Bossa

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…Several other human cancers are associated with chromosome 3p allele loss including small and non-small lung cell carcinoma, uterine and breast cancer. Recently, Naylor et al (1989) and Erlandsson et al (1990) have independently isolated the same gene from chromosome 3p21…”

Section: Familial Renal Cell Carcinoma Without Additionalfeaturesmentioning

confidence: 99%

Familial renal cell carcinoma: clinical and molecular genetic aspects

Maher,

Yates

1991

Br J Cancer

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Summary Renal cell carcinoma (RCC) accounts for 2% of all human cancer, but familial cases are infrequent. Riches (1963) andGriffin et al. (1967) found only 1% of cases were familial in their respective series. McLaughlin et al. (1984) in a population-based case-control study found a family history of renal cell carcinoma in 2.4% of affected patients compared to 1.4% of controls. Nevertheless the importance of inherited tumours in clinical practice and medical research is disproportionate to their frequency. In clinical practice recognition of familial RCC can provide opportunities to prevent morbidity and mortality by appropriate screening. In medical research recent advances in molecular genetics offer the prospect of isolating the genes involved in the pathogenesis of familial RCC and of the more common sporadic cases. In this article we review the clinical and molecular genetics of inherited renal cell carcinoma (adenocarcinoma or hypernephroma). Clinical aspectsAs with other inherited tumours, familial RCC is characterised by (i) an early age at onset compared to sporadic cases, (ii) frequent bilaterality and (iii) multicentricity. Mean age at diagnosis in familial cases is about 45 years, more than 15 years earlier than for sporadic cases (Maher et al

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“…The absence of human AAP function has also been correlated with cell proliferation in small-cell lung carcinomas and renal carcinomas (Erlandsson et al, 1991;Naylor et al, 1989), but the potential role of the enzyme in the malignant state of these cell lines has not been established. More recently, acylaminoacyl peptidase in porcine brain has been shown to be a more sensitive target for organophosphorus compounds than acetylcholinesterase (Richards & Lees, 2002;Duysen et al, 2001) and hence may be a potential site for cognitive-enhancing compounds (Richards et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase

et al. 2005

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Acylaminoacyl peptidase (also known as acylamino-acid-releasing enzyme or acylpeptide hydrolase; EC 3.4.19.1) is an unusual member of the prolyl oligopeptidase family catalysing the hydrolysis of an N-acylated peptide to an acylamino acid and a peptide with a free N-terminus. Acylaminoacyl peptidase purified from porcine liver has been crystallized in mother liquor containing 0.1 M Tris-HCl pH 7.0, 10%(w/v) polyethylene glycol 8000, 50 mM MgCl 2 and 1%(w/v) CHAPS using the hanging-drop vapour-diffusion technique. A full data set to 3.4 Å resolution was collected at ESRF beamline ID14-4 and space group C222 was assigned, with unit-cell parameters a = 84.8, b = 421.1, c = 212.0 Å and four molecules in the asymmetric unit.

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The DNF15S2 locus at 3p21 is transcribed in normal lung and small cell lung cancer

Cited by 52 publications

References 16 publications

Genetic relationship between acylpeptide hydrolase and acylase, two hydrolytic enzymes with similar binding but different catalytic specificities.

Genetic relationship between acylpeptide hydrolase and acylase, two hydrolytic enzymes with similar binding but different catalytic specificities.

Familial renal cell carcinoma: clinical and molecular genetic aspects

Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase

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